Saphenous vein grafts remain an important conduit for surgical coronary revascularization. These conduits, however, have limited durability. The mechanisms for vein graft failure include inflammation and intimal injury followed by smooth muscle cell proliferation and intimal thickening. Recently, ex vivo genetic modification of vein grafts has achieved interruption of some of the steps in this complex mechanism. In this project, we propose to transfect vein grafts with two different genes in an effort to affect different steps in the process of vein graft failure. The beta-adrenergic receptor kinase carboxyl terminus (BARKct) is a peptide, which binds G-protein beta gamma subunits and thereby prevents activation of Ras/MAP kinase pathways involved in smooth muscle cell proliferation. Nitric oxide (NO) is an important mediator for endothelial function, which has been shown to be disrupted during the process of vascular grafting. Successful transfection of the endothelial NO synthase (eNOS) gene in saphenous vein grafts preserves NO production. Cotransfection of vein grafts with both of these genes (BARKct and eNOS) at the time of surgery may reduce intimal hyperplasia, preserve endothelial function, and thereby prevent vein graft failure.